The mechanisms of reduced analgesic effect of morphine in neuropathic pain

吗啡对急性疼痛有很强的镇痛作用，但对神经性疼痛却不那么有效。吗啡腹腔注射对正常大鼠和SNL大鼠均有镇痛作用，但对正常大鼠的镇痛作用更大。吗啡通过激活颈侧腹内侧髓质5-羟色胺能神经元增加脊髓背角的5-羟色胺释放，而非去甲肾上腺素释放。昂丹司琼或硫酸5,7-二羟色胺肌酐鞘内预处理对正常大鼠吗啡的镇痛作用减弱，对SNL大鼠吗啡的镇痛作用增强。全身给药吗啡使脊髓内5-HT水平升高，在正常状态下，5-HT的升高有助于吗啡诱导的镇痛，但在神经性疼痛中，5-HT通过脊髓5-HT3受体减弱镇痛。下降的血清素能系统的可塑性可能有助于降低全身性吗啡对神经性疼痛的疗效。

Morphine produces powerful analgesic effects against acute pain, but it is not as effective against neuropathic pain. Intraperitoneal administration of morphine produced analgesic effects in normal and SNL rats, but the effects were greater in normal rats. Morphine increased 5-HT release, but not noradrenaline release, in the spinal dorsal horn via activation of serotonergic neurons in the rostral ventromedial medulla. Intrathecal pretreatment with ondansetron or 5,7-dihydroxytryptamine creatinine sulfate attenuated the analgesic effect of morphine in normal rats but increased the analgesic effect of morphine in SNL rats.Systemic administration of morphine increases 5-HT levels in the spinal cord, and the increase in 5-HT contributes to morphine-induced analgesia in the normal state, but attenuates that in neuropathic pain through spinal 5-HT3 receptors. The plasticity of the descending serotonergic system may contribute to the reduced efficacy of systemic morphine in neuropathic pain.